In the art of growing anchorage-dependent cell tissue cultures, it has heretofore been proposed to replace the standard roller bottles and petrie dishes with so-called microcarriers for providing enhanced surface area for cell attachment. The U.S. patent to Levine et al No. 4,189,534 proposes, for example, the microcarriers in the form of solid plastic beads be employed. It has been found, however, that plastic microcarriers of this type require alteration of electrically charged surface moieties to promote cell attachment, which alteration is difficult to control quantitatively in production and is toxic to some types of cell cultures if not properly controlled. It is also difficult to remove some cell types from the plastic bead surface.
It has also been proposed to employ solid glass beads as cell microcarriers. In addition to the aforementioned problems, a significant disadvantage of microcarriers previously proposed, including specifically solid beads of plastic or glass, is a difficulty in controlling or tailoring the density of the microcarrier to that of the selected culture medium. Conventional cell culture media are aqueous in nature and possess densities generally in the range of 1.03 to 1.09 g/cc. Silica glass beads, which possess desirable surface qualities, typically have a density on the order of 2.3 g/cc depending upon glass composition. To avoid settling and compaction of the microcarriers in the growth medium, which tends to inhibit cell growth, it is necessary to stir or otherwise continuously agitate the culture medium. However, vigorous agitation is itself destructive to many cell types. The art relating to microcarriers for animal cell cultures in general is reviewed in 3rd General Meeting of ESACT, Oxford 1979, Develop, biol. Standard, 46, pp, 109-294 (S. Karger, Basel 1980).
In the copending U.S. application of Downs et al, Ser. No. 332,377, filed Dec. 21, 1981 and assigned to the assignee hereof, the foregoing and other difficulties in the art are addressed by forming hollow glass precursor microspheres of silicate glass composition, and then tailoring the density of such precursor microspheres in a post-forming etching operation to match closely the density of the desired aqueous growth medium. This technique has proven successful in overcoming both the surface-charge and the buoyancy problems of the earlier art. However, the number of separate operations involved makes cost reduction desirable.